2,4-Dimethoxybenzylamine → 7-bromo-2-(2,4-dimethoxybenzyl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one

HRID 1055978Notes

Reaction equation

HRID 1055978 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[C:7]([O:9][CH3:10])[CH:6]=[CH:5][C:4]=1[CH2:11][NH2:12].[Br:13][C:14]1[CH:15]=[C:16]([C:22](OC)=[O:23])[N:17]([CH2:19][CH2:20]Br)[CH:18]=1>CS(C)=O>[Br:13][C:14]1[CH:15]=[C:16]2[C:22](=[O:23])[N:12]([CH2:11][C:4]3[CH:5]=[CH:6][C:7]([O:9][CH3:10])=[CH:8][C:3]=3[O:2][CH3:1])[CH2:20][CH2:19][N:17]2[CH:18]=1

Participants

4

Reactant 2

HCID 5972502,4-DimethoxybenzylamineHCID 89783682methyl 4-bromo-1-(2-bromoethyl)-1H-pyrrole-2-carboxylate

Product 1

HCID 897836627-bromo-2-(2,4-dimethoxybenzyl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-oneYield 85.3%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
150 °C

Procedure

(2,4-Dimethoxyphenyl)methanamine (Aldrich; 4.36 mL, 28.9 mmol) was added to a stirred solution of methyl 4-bromo-1-(2-bromoethyl)-1H-pyrrole-2-carboxylate (Example 165a; 3.60 g, 11.58 mmol) in DMSO (15 mL) at RT. The reaction was heated at 150° C. in an oil bath for 5 h. After it was cooled to RT, the brown mixture was partitioned between 10 mL of 2.0 N aq. HCl and 200 mL of EtOAc. The layers were separated; the organic solution was washed with 2.0 N aq. HCl (5 mL) followed by brine (5 mL), dried (Na2SO4), and concentrated. Purification on a silica gel column (25-75% EtOAc in Hexanes) gave 7-bromo-2-(2,4-dimethoxybenzyl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one (3.61 g, 9.88 mmol, 85% yield) as an off-white crystalline solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.15 (1H, d, J=1.8 Hz), 7.11 (1H, d, J=8.2 Hz), 6.68 (1H, d, J=1.8 Hz), 6.59 (1H, d, J=2.3 Hz), 6.50 (1H, dd, J=8.3, 2.4 Hz), 4.53 (2H, s), 4.12 (2H, dd, J=6.7, 5.2 Hz), 3.81 (3H, s), 3.76 (3H, s), 3.57 (2H, dd, J=6.7, 5.0 Hz). m/z (ESI, +ve) 365/367 (M+H)+.

Workup

  1. temperatureAfter it was cooled to RT
  2. customthe brown mixture was partitioned between 10 mL of 2.0 N aq. HCl and 200 mL of EtOAc
  3. customThe layers were separated
  4. washthe organic solution was washed with 2.0 N aq. HCl (5 mL)
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customPurification on a silica gel column (25-75% EtOAc in Hexanes)

Sources & evidence

ORD record
ord-6de585ca2430441a8c2a9e41c202be71
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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